美国食品和药物管理局已批准了多种治疗晚期转移性肾细胞癌的药物，包括抗血管酪氨酸激酶抑制剂（TKI）和免疫检查点抑制剂（ICIs）。一线治疗的选择包括单一疗法或联合疗法。然而，选择合适的一线和二线治疗方法来提高总生存期仍然是一个悬而未决的问题。 评估转移性透明细胞肾细胞癌（mRCC）患者的总生存期（OS）和无进展生存期（PFS） 。根据TKI和抗PD-1给药的治疗顺序将患者分为几组。根据抗 PD-1 和 TKI 的给药顺序评估总体生存获益。在这项回顾性倾向匹配队列研究中，我们确定了自 1 月 1 日起在山东第一医科大学附属肿瘤医院接受治疗的 135 名 mRCC 患者。 2017年至2022年12月31日。这些患者接受了抗PD-1治疗作为一线或二线治疗的一部分。统计分析于2023年6月1日至2023年8月1日进行。主要结局指标是OS，从诊断日期到死亡或最后一次随访。治疗期间监测 PFS。使用 Cox 比例风险回归和 Kaplan-Meier 估计进行生存分析。通过比较患者的完整治疗疗程，根据免疫治疗线数比较不同组患者的生存情况。最终队列由 135 名患者组成，其中 84 名接受抗 PD-1 一线治疗（包括 6 名患者）单独接受抗 PD-1（替雷利珠单抗、卡瑞利珠单抗、特瑞普利单抗或信迪利珠单抗）治疗的患者和 78 名接受抗 PD-1 联合抗血管 TKI（阿西替尼、舒尼替尼、索凡替尼或帕唑帕尼）治疗的患者。其余 51 名患者在初始 TKI 治疗方案后接受抗 PD-1 作为二线治疗。患者最初根据一线治疗中是否使用抗 PD-1 药物进行分类。研究发现，接受一线靶向治疗的患者的 OS 高于接受一线免疫治疗的患者，中位 OS 分别为 33 个月和 15 个月。为了进一步研究这一结果，我们根据治疗方案中抗 PD-1 和 TKI 的给药顺序细化了患者组。我们发现一线 TKI 联合抗 PD-1 治疗的患者的中位 PFS 为 3.5 个月，而一线 TKI 后 TKI 联合抗 PD-1 治疗的患者中位 PFS 为 14.5 个月 (p=0.0092)。二线治疗的中位 PFS 为 6.5 个月 vs 15 个月 (p=0.0014)。同样，中位 OS 分别为 16.66 个月和 31.88 个月 (p=0.008)。这项研究表明，与其他治疗序列相比，在抗血管治疗后进行免疫治疗可显着提高 OS 和 PFS。这一发现为有关治疗测序的临床决策提供了宝贵的见解和强大的数据支持。© 作者。

The Food and Drug Administration of the United States has approved several drugs for treating advanced metastatic renal cell carcinoma, including anti-vascular tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). Options for first-line therapy include monotherapy or combination therapy. However, selecting a suitable first-line and second-line treatments to improve overall survival remains an unresolved issue.To evaluate the overall survival (OS) and progression-free survival (PFS) of patients with metastatic clear cell renal cell carcinoma (mRCC). Patients were divided into several grouped according to the treatment sequence of TKI and anti PD-1 administration. The overall survival benefit was evaluated based on the order of administration of anti PD-1 and TKI.In this retrospective propensity-matched cohort study, we identified 135 patients with mRCC treated at the Affiliated Cancer Hospital of Shandong First Medical University from January 1, 2017, to December 31, 2022. These patients had received anti PD-1 treatment as part of their first or second line of therapy. Statistical analysis was performed from June 1, 2023, to August 1, 2023. The primary outcome measure was OS, from the date of diagnosis to death or the last follow-up. PFS was monitored during treatment. Survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates. By comparing the complete treatment course of patients, the survival of patients in different groups was compared according to the number of immunotherapy lines.The final cohort comprised 135 patients, of whom 84 received first-line therapy with anti PD-1 (include 6 patients treated with anti PD-1 (tislelizumab, carrelizumab, toripalimab or sintilizumab) alone and 78 patients treated with anti PD-1 combined with anti-vascular TKI (axitinib, sunitinib, solfanitinib or pazopanib)). The remaining 51 patients were treated with anti PD-1 as second-line therapy following an initial regime of TKIs. Patients were initially categorized based on whether anti PD-1 were used in the first-line treatment. It was observed that the OS of patients receiving first-line targeted therapy was higher than those receiving first-line immunotherapy, with a median OS of 33 months versus 15 months. To investigate this outcome further, we refined the patient groups based on the administration sequence of anti PD-1 and TKIs in the treatment regimen. We found that the median PFS of patients with first-line treatments of TKI combined with anti PD-1 was 3.5 months, compared to 14.5 months when TKI combined with anti PD-1 followed first-line TKI (p=0.0092). The median PFS for second-line treatments was 6.5 months versus 15 months (p=0.0014). Similarly, the median OS was 16.66 months and 31.88 months, respectively (p=0.008).This study indicates that administering immunotherapy following anti-vascular therapy significantly enhances both OS and PFS compared to other sequences of therapies. This finding provides valuable insights and robust data support for clinical decision-making regarding treatment sequencing.© The author(s).